Pesticide Toxicity - Adam Oliver Brown

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BIO4101 – Pesticides and the environment

Pesticide Toxicity


Measures of Toxicity

●  Any chemical is toxic in the right dose –  e.g. common table salt can kill a human – Therefore, almost all pesticides are toxic

●  Toxicity: inherent capacity of a substance to produce injury or death of an organism


Dihydrogen monoxide

●  Death from inhalation ●  Tissue damage from prolonged exposure ●  Major component of acid rain ●  Gas can cause severe burns ●  Found in carcinogenic biopsies ●  Associated with school-yard violence ●  www.dhmo.org


Measures of Toxicity

●  Acute toxicity: toxicity due to short term exposure (24-96hr)

●  Subchronic toxicity: toxicity due to a short term exposure (3-6 months)

●  Chronic toxicity: Toxicity due to long term exposure (years, lifespan, generations)


Laboratory toxicological studies Development of

regulatory options

Evaluation of public health, environmental, economic,

social, and political consequences of regulatory options

Extrapolation methods

Exposure characterization

ANALYSIS Effect

charactertization Epidemiology and population-level

studies

Measurements of exposure and

dose

Problem Formulation and Hazard Identification

Risk Characterization

DATA GATHERING RISK ASSESSMENT RISK MANAGEMENT

Identification of mitigation options

Research needs identified

Regulatory decision

Risk communication

Regulatory Process (PMRA)


EXPOSURE TOXICITY TOXICITY

PROBABILITY

RISK

Assessment of hazard based on a

ratio of single deterministic exposure and toxicity values

Ranking of concerns in the

absence of specific exposure

information

Assessment of risk based on likelihood of exposure and/or

toxicity

TOXICITY EXPOSURE

Process of Risk Assessment

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Health Risk Assessment (humans) ●  Toxicity ratings based on

data from experimental animals – No data from humans except

accidental ●  Usually expressed as LD50

(sometimes LC50) – Lethal dose (concentration) to

50% of experimental population

– Expressed as mg/kg (or ppm)


Example: LD50 = 10 ●  10mg of pesticide applied to animals

weighing 1kg, it would kill 50% of experimental population


Concentration Response of Fish to DDT

C

Concentration

LC50

99.9 99 90 70

100

30 10

1 0.1

Perc

ent m

orta

lity


Same LD50 but Different Slopes Pe

rcen

t mor

talit

y B A

LC50 LC99

99.9 99

90 70

30 10

1 0.1

50

100


Substances Considered Highly Toxic ●  Oral Toxicity:

–  Produces death in ≥50% of animal population upon administering 50mg orally per kg of body weight in a single dose

●  Toxicity on Inhalation: –  Produces death in ≥50% of animal population at dose

of 200ppm or less (continuous inhalation for 1hr or less)

●  Toxicity by Skin Absorption: –  Produces death in ≥50% of animal population (rabbits

only) at a dose of 200mg/kg (continuous contact for 24hrs or less)


Hazard Ratings

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Other Tests for Health Risk Assessment

●  Mutagenesis tests ●  Sub-chronic oral toxicity

– Objective: to find the No Observed Effect Level ●  Multi-generation reproduction studies ●  Teratology (foetal development) ●  Chronic oral toxicity (over lifetime)


Acute Oral Lethal Dose Toxin Type Amount for 70kg person Botulinus toxin Microbial 0.000000014 g Parathion Insecticide 0.14 g Nicotine Insecticide 3.7 g DDT Insecticide 8.1 g Caffeine Food 13.4 g Codeine Pharmaceutical 42 g 2,4-D Herbicide 42 g Malathion Insecticide 54 g Aspirin Pharmaceutical 95 g Atrazine Herbicide 126 g Salt Food 300 g Glyphosate Herbicide 350 g Sugar Food 3000 g

Table 49


Guidelines ●  Connotation of “highly toxic” does not

mean it is not used ●  Therefore guidelines are provided (EPA,

PMRA) – Application procedure – Dosage – Ventilation – Exposure…


Misuse of Pesticides


PHI

MRL

0 2 4 6 8 10 12 Days after application

0.1

1.0

10

Con

cent

ratio

n of

the

pest

icid

e in

the

crop

(mg/

kg)

Residue Limits and Pre-Harvest Interval

Fig. 191


PHI Variations in Dissipation Rates Food Pesticide Pest PHI (days) Celery Carbaryl Leafhopper 3 Corn Carbaryl Corn Borer 1 Lettuce Dimethoate Aphid 7 Pepper Dimethoate Aphid 30 Apple Captan Apple scab 7 Cherry Captan Brown rot 2

●  Properties of pesticides and environmental conditions –  Hydrolysis, photodecomposition, vaporisation

●  Metabolism on surface and inside plant –  Enzymes & micro-organisms

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100

0 Dose

LOAEL NOAEL

Best-fitting dose- response model

Lower confidence interval on line

% o

f ani

mal

s re

spon

ding

No Observed Adverse Effect Level


Acceptable Daily Intake

ADI (mg/kg) human = NOAEL (animal)

Safety factor (100)

From To Uncertainty Factor Average Sensitive human >10 Animal Human >10 Database inadequacies >10

US EPA guidelines


Maximum Permissible Levels

MPL (mg/kg) food = ADI x 60kg

Food factor

Food Food Factor (kg/day) Vegetable/Fruit 0.4 Milk & products 0.5 Corn & products 0.2 Meat & products 0.2

For average North American


For example: Endosulfan insecticide

MPL (mg/kg) fruit/veg = 0.0075 x 60kg

0.4 = 1.12 mg/kg

●  This number is THE LAW ●  It is inspected in the field by PMRA and elsewhere in

delivery chain, customs by CFIA ●  Enforceable for all products produced and sold in the

country (even imports) ●  Detected levels usually far below MPLs ●  Detection tools by GC/MS sophisticated to ppm/ppb


Transport and Fate in the Environment

Short distance Long distance Degradation

Photodegradation

Erosion

Biological degradation

Crop removal

Long distance transport of dust and vapor

Volatilization

DESORBED

Erosion

Runoff

Biological degradation Leaching

ADSORBED

SOIL Water table

Photolysis Transport of

residue in fish

Transport

Uptake Chemical

degradation

Uptake

Adsorption and exudation

Sedimentation

WATER Resuspension

Volatilization

Adsorption- desorption

Transport of residues in birds

Precipitation of rain and dust

AIR Precipitation of

rain and dust Dust storm

Spray drift

Fig. 158


Bioaccum/magnification Potential ●  1) Amount available to organism from

environment – Persistence, transportability, dosage

●  2) Rate of intake by organism – Concentration in environment, quantity

organism consumes over time ●  3) Rate of elimination by organism

– Metabolism, rate at which metabolites produced, lipophilicity

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Metabolic Degradation

Chemical bound as a terminal residues in

proteins, cellulose or lignin (only in plants)

Conjugated chemical

Detoxified chemical

(less toxic)

Chemical Phase-1 metabolism

Phase-2 metabolism

Phase-3 metabolism

Excretion

Excretion

Excretion

Fig. 130


Enzymatic Detoxification

Binds to enzyme at the site of action and causes toxic effect

PESTICIDE

Enzyme for phase-1 metabolism

Enters organism

PHASE-1 Enzyme PHASE-2

OH

COOH

NH 2

HS

O-sugar

N-sugar

S-amino acid

COO-amino acid Fig. 131


Effects of Lipophilicity

Water solubility

High Kd

Low Kd

Ads

orpt

ion

Fig. 160

Water solubility in µg/L (log scale)

Bio

mag

nific

atio

n in

fis

h (lo

g sc

ale)

Fig. 168


Pesticide Breakdown ●  Persistence = ability to resist breakdown ●  Environmental degradation of pesticides

occurs principally via: –  1) microorganisms –  2) photochemical breakdown


Microbial Degradation ●  Diversity of microbial species in soil

allows for a wide variety of organic molecules to be catabolized

●  Particularly bacteria and fungi ●  Dependent on temperature, moisture, pH,

aeration, solubility of chemical


Effects of pH on Adsorption in Soil

pH 3.5 6 9

Kd

Fore

st

Agr

icul

tura

l

Fig. 161

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Microbial Degradation: metabolites

●  Slight modifications in chemical structure can change persistence dramatically –  e.g. 2,4-D and 2,4,5-T differ only by

chlorinated side group –  2,4-D is readily broken down but 2,4,5-T is

highly persistent


Toxic Metabolites ●  Intermediate or end-point metabolites

may be more toxic than originals ●  The photochemical breakdown of

chlorinated compounds may lead to the production of dioxins – Polychlorinated dibenzodioxins (PCDD) – Lipophilic mutagens and carcinogenic


2,4,5-T and 2,4-D with their Dioxins

C l C l

C l C l

O N a C l

C l C l

O C l

C l C l

C H 2 C O H O

O N a C l

C l C l +

O O

C l C l

C l C l

O C l C l C l

C l

C l C H 2 C O H O

N a O H Benzene 2,4,5-T

2,3,7,8,-TCDD Chlorinated Furan

Heat

C l 2 O H O H

C l

C l

O C l

C l

C H 2 C O H O

O H C l

C l

C l

O O

C l C l

O C l O

C l

C l C l

C l C H 2 C O H O

N a O H Phenol 2,4-D

2,8-dichlorodioxin

Heat

C l 2

N a O H Heat N a O H

1,3,6,8-TCDD

Fig. 173 Fig. 174


Photochemical Degradation ●  There exist sufficient energy in ultraviolet

component of sunlight (290-450 nm) to cause a number of chemical reactions: – Oxidation, reduction, isomerization,

elimination etc…


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Pesticide Toxicity - Adam Oliver Brown